Erlend Mork

Suicidality before and in the early phases of first episode psychosis

INTRODUCTION The suicide risk in psychotic disorders is highest in the early phases of illness. Studies have typically focused on suicidality from treatment start rather than actual onset of psychosis. This study explored the prevalence and characteristics of suicidality in patients with a first episode of psychosis (FEP) in two time intervals: 1) prior to study entry and 2) explicitly in the period of untreated psychosis. METHOD One hundred seventy FEP-patients were interviewed as soon as possible after treatment start. The interview included assessments of diagnoses, suicidality, symptoms, substance use, and premorbid functioning. RESULTS Nearly 26% of the patients attempted suicide prior to study entry and 14% made suicide attempts during the period of untreated psychosis. Of the patients who had been suicidal (i.e. experienced suicidal ideation or attempts), 70% were suicidal during the period of untreated psychosis. Suicide attempts prior to study entry were associated with female gender, more depressive episodes, younger age at psychosis onset, and history of alcohol disorder. Suicide attempts during untreated psychosis were also associated with more depressive episodes and younger age at illness onset, in addition to drug use the last six months and longer duration of untreated psychosis (DUP). CONCLUSION The prevalence of suicidality before and in the early phases of FEP is high, especially during untreated psychosis. As prolonged DUP is associated with suicide attempts during the period of untreated psychosis, reducing the DUP could have the effect of reducing the prevalence of suicide attempts in patients with FEP.

Suicidality in first episode psychosis is associated with insight and negative beliefs about psychosis

INTRODUCTION Suicidal behaviour is prevalent in psychotic disorders. Insight has been found to be associated with increased risk for suicidal behaviour, but not consistently. A possible explanation for this is that insight has different consequences for patients depending on their beliefs about psychosis. The present study investigated whether a relationship between insight, negative beliefs about psychosis and suicidality was mediated by depressive symptoms, and if negative beliefs about psychosis moderated the relationship between insight and suicidality in patients with a first episode of psychosis (FEP). METHOD One hundred ninety-four FEP-patients were assessed with a clinical interview for diagnosis, symptoms, functioning, substance use, suicidality, insight, and beliefs about psychosis. RESULTS Nearly 46% of the patients were currently suicidal. Depressive symptoms, having a schizophrenia spectrum disorder, insight, and beliefs about negative outcomes for psychosis were independently associated with current suicidality; contradicting a mediating effect of depressive symptoms. Negative beliefs about psychosis did not moderate the effect of insight on current suicidality. CONCLUSION The results indicate that more depressive symptoms, higher insight, and negative beliefs about psychosis increase the risk for suicidality in FEP-patients. The findings imply that monitoring insight should be part of assessing the suicide risk in patients with FEP, and that treating depression and counteracting negative beliefs about psychosis may possibly reduce the risk for suicidality.

High prevalence of childhood trauma in patients with schizophrenia spectrum and affective disorder

OBJECTIVE Childhood trauma (CT) is a major risk factor for various psychiatric disorders. We wanted to determine the prevalence of CT in a catchment area-based sample of schizophrenia spectrum and affective disorder (including bipolar disorder and depressive episodes with psychotic features) and to explore potential differences in types of CT between the diagnostic groups. METHOD Three hundred five patients were recruited consecutively from psychiatric units at 3 major hospitals in Oslo, Norway, diagnosed with Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Traumatic childhood events were assessed with Childhood Trauma Questionnaire. RESULTS Eighty-two percent of the patients had experienced one or more CT events, the most frequent subtype of trauma being emotional neglect. The schizophrenia spectrum group reported significantly more physical abuse and physical neglect than the affective group. CONCLUSION A high prevalence of CT in patients with severe mental disorder was detected. This reminds us of the importance of exploring this issue when we treat such patients. The mechanisms behind these differences are unclear. Further research is needed to study potential associations between CT and the clinical picture of the disorder.

Increased Systemic Cortisol Metabolism in Patients With Schizophrenia and Bipolar Disorder: A Mechanism for Increased Stress Vulnerability?

OBJECTIVE The hypothalamic-pituitary-adrenal (HPA) axis seems dysregulated and part of the pathophysiology in bipolar disorder and schizophrenia, but the underlying mechanisms are unknown. Recent evidence indicates that systemic cortisol metabolism influences blood cortisol levels and HPA axis functioning. Our objective was to estimate systemic cortisol metabolism by means of the activity of 5α-reductase, 5β-reductase, and 11β-hydroxysteroid dehydrogenase (11β-HSD) in patients with bipolar disorder and schizophrenia spectrum disorders compared to healthy controls. METHOD Inpatients and outpatients aged 18 to 65 years with DSM-IV bipolar disorder (n = 69) or schizophrenia (n = 87) were consecutively recruited to the catchment area-based Thematically Organized Psychosis Research (TOP) study. Healthy controls (n = 169) were randomly selected from statistical records from the same catchment area and were contacted by letter inviting them to participate. Spot urine samples were collected in a cross-sectional manner from November 2006 to November 2008. Urinary free cortisol and cortisone and their metabolites were analyzed with liquid chromatography tandem mass spectrometry and used as indicators of 5α-reductase, 5β-reductase, and 11β-HSD activity. RESULTS The combined patient group had increased activity of 5α-reductase, 5β-reductase, and 11β-HSD2 (all P < .001) compared to controls. Elevated systemic cortisol metabolism was present in both schizophrenia (5α-reductase, 5β-reductase, and 11β-HSD2; all P < .001) and bipolar disorder (5α-reductase [P = .016], 5β-reductase [P = .001], and 11β-HSD2 [P = .007]). CONCLUSIONS The results indicate increased activity of cortisol metabolism in patients with bipolar disorder and schizophrenia compared to healthy controls and suggest that increased systemic cortisol metabolism is involved in the pathophysiology and stress vulnerability in these severe mental disorders. The findings should be explored further in terms of potential new drug targets, and they add to the physiologic rationale for stress coping strategies in these patient groups.

Patterns of childhood adverse events are associated with clinical characteristics of bipolar disorder

BackgroundPrevious studies in bipolar disorder investigating childhood trauma and clinical presentations of the illness have mainly focused on physical and sexual abuse. Our aim was to explore further the relationship between childhood trauma and disease characteristics in bipolar disorder to determine which clinical characteristics were most strongly associated with childhood trauma total score, as well as subtypes of adverse childhood events, including physical, sexual, emotional abuse and neglect.Methods141 Patients with bipolar disorder were consecutively recruited, and disease history and clinical characteristics were assessed. History of childhood abuse was obtained using the Childhood Trauma Questionnaire (CTQ). Statistical methods used were factor analysis, Poisson and linear regression, and generalized additive modeling (GAM).ResultsThe factor analysis of CTQ identified three factors: emotional abuse/neglect, sexual abuse and physical abuse. There were significant associations between CTQ total score and earlier onset of illness, reduced level of psychosocial functioning (GAF; Global Assessment of Functioning) and decreased number of hospitalization, which mainly were due to the factor emotional abuse/neglect. Physical abuse was significantly associated with lower GAF scores, and increased number of mood episodes, as well as self-harm. Sexual abuse was significantly associated with increased number of mood episodes. For mood episodes and self-harm the associations were characterized by great variance and fluctuations.ConclusionsOur results suggest that childhood trauma is associated with a more severe course of bipolar illness. Further, childhood abuse (physical and sexual), as well as emotional abuse and neglect were significantly associated with accelerating staging process of bipolar disorder. By using specific trauma factors (physical abuse, sexual abuse and emotional abuse/neglect) the associations become both more precise, and diverse.

Age at onset of bipolar disorder in a Norwegian catchment area sample.

BACKGROUND Early onset of bipolar disorder (BD) is an important clinical predictor of a more severe course and poorer outcome. A higher proportion of childhood onset BD has been reported in studies from USA compared to Europe. We investigated age at onset of first affective episode in a Norwegian sample and compared it to previous European and US findings. In addition, we examined whether age at onset influenced on time to first treatment, and if patient characteristics related to illness severity influenced age at onset. METHODS Two hundred and twenty five BD patients were recruited consecutively mainly from psychiatric out-patient units at three major hospitals in Oslo, Norway, diagnosed using SCID-I and divided into four groups based on age at onset. RESULTS Six percent of the patients had onset in childhood, 32% in adolescence, 43% in young adulthood, and 19% as adults. Average age at onset was 22.8 years (SD 9.4). There was a significantly higher age at onset and a significantly shorter time from onset to first treatment in patients with lifetime hospitalization. LIMITATION Retrospective information which could be confounded by collection bias. CONCLUSION Age at onset in our sample resembled previous European studies, but not US- or Norwegian studies. The difference in age at onset seems more related to different definitions of onset, than to hospitalization history. This highlights the importance of improving the research criteria and of using similar criteria to ascertain age at onset.

The development of insight and its relationship with suicidality over one year follow-up in patients with first episode psychosis

OBJECTIVE Insight into psychosis has been linked to suicidality, although inconsistently. The co-variation between insight and suicidality over time is under-investigated. The aim of the present study was to investigate predictors of suicidality in patients with first episode of psychosis (FEP) over one year, focusing on the relationship between insight and suicidality. METHODS Patients with FEP (n=146) were interviewed as soon as possible after treatment starts and at one year follow-up. RESULTS At baseline 37% of patients were suicidal, significantly reduced to 20% at follow-up. The effect of insight on suicidality was in different directions at different time-points, with insight at baseline increasing and insight at follow-up decreasing the risk of suicidality at follow-up. Patients with stable levels of insight across baseline and follow-up did not differ in risk for suicidality at follow-up. However, patients who lost insight from baseline to follow-up were more often suicidal at follow-up, whilst patients who gained insight were more seldom suicidal at follow-up. Other predictors of suicidality at follow-up were more depressive episodes before study entry, longer duration of untreated psychosis, more suicide attempts six months prior to follow-up, and depression at follow-up. CONCLUSION The results indicate that the effect of insight on suicidality in FEP-patients depends on time of assessment and of changes in insight. Gaining insight during treatment was associated with reduced risk for suicidality, whilst losing insight had the opposite effect, underlining the need to monitor insight over time and tailor interventions according to illness phase.

Neurocognitive functioning and suicidality in schizophrenia spectrum disorders

OBJECTIVE The aim of this study was to investigate whether suicide attempters had higher IQ, better executive functioning, or were more impulsive as measured by neuropsychological tests than non-attempters in a group of patients with schizophrenia spectrum disorders. METHOD One hundred seventy-four patients with schizophrenia spectrum disorders were assessed with a clinical interview for diagnosis, suicidality, symptoms and function, and underwent an extensive neurocognitive test battery. RESULTS There were no statistically significant differences in any neurocognitive domains between lifetime suicide attempters and non-attempters, or between patients with different rates of suicide attempts. Currently suicidal patients were significantly more impulsive (had poorer inhibitory control) than currently non-suicidal patients, but this difference was mediated by positive psychotic symptoms. CONCLUSION The findings indicate that among patients with schizophrenia spectrum disorders, there are no significant differences in IQ or neurocognitive functioning between suicide attempters and non-attempters.

SRD5A2 is associated with increased cortisol metabolism in schizophrenia spectrum disorders

OBJECTIVE Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is documented in bipolar disorder and schizophrenia, but the mechanism is unclear; recently, increased activity of cortisol metabolizing enzymes was indicated in these disorders. We investigated whether five genes involved in cortisol metabolism were associated with altered activity of cortisol metabolizing enzymes in bipolar disorder (BD) and schizophrenia spectrum disorders (SCZ). METHODS A case-control sample of subjects with BD (N=213), SCZ (N=274) and healthy controls (N=370) from Oslo, Norway, were included and genotyped from 2003 to 2008. A sub-sample (healthy controls: N=151; SCZ: N=40; BD: N=39) had estimated enzyme activities based on measurements of urinary free cortisol, urinary free cortisone and metabolites. A total of 102 single nucleotide polymorphisms (SNPs) in the SRD5A1, SRD5A2, AKR1D1, HSD11B1 and HSD11B2 genes were genotyped, and significant SNPs analyzed in the sub-sample. RESULTS There was a significant association of rs6732223 in SRD5A2 (5α-reductase) with SCZ (p=0.0043, Bonferroni corrected p=0.030, T risk allele). There was a significantly increased 5α-reductase activity associated with rs6732223 (T allele) within the SCZ group (p=0.011). CONCLUSIONS The present data suggest an interaction between SCZ and SRD5A2 variants coding for the enzyme 5α-reductase, giving rise to increased 5α-reductase activity in SCZ. The findings may have implications for cortisol metabolizing enzymes as possible drug targets.

Self-Harm in Patients with Schizophrenia Spectrum Disorders

This study describes the prevalence, clinical characteristics, and gender profile of self-harm in a cross-sectional sample of 388 patients with schizophrenia spectrum disorders. All patients were interviewed and assessed with respect to lifetime self-harm and relevant clinical variables. An overall of 49% of the patients reported self-harm which was associated with female gender, having had a depressive episode, younger age at psychosis onset, alcohol abuse or dependence, current suicidality, awareness of illness, and low adherence to prescribed medication. Higher awareness of having a mental disorder was associated with self-harm in men only, while emotional dysregulation was associated with self-harm in women only. We conclude that while self-harm in patients with schizophrenia spectrum disorders is highly prevalent in both genders, risk factors in men and women differ in several important ways.